Haploidentical Bone Marrow Transplantation with Post-Transplantation Cyclophosphamide Plus Thiotepa Improves Donor Engraftment in Patients with Sickle Cell Anemia: Results of an International Learning Collaborative
Haploidentical Bone Marrow Transplantation with Post-Transplantation Cyclophosphamide Plus Thiotepa Improves Donor Engraftment in Patients with Sickle Cell Anemia: Results of an International Learning Collaborative
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DOI：
10.1016/j.bbmt.2018.11.027
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发表时间：
2019-06-01
影响因子：
4.3
通讯作者：
Kassim, Adetola A.
中科院分区：
文献类型：
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作者：
de la Fuente, Josu;Dhedin, Nathalie;Kassim, Adetola A.
对于患有严重镰状细胞病（SCD）且缺乏相同hla的兄弟姐妹供体的个体的治疗一直令人沮丧地难以捉摸。为了改善移植，同时最大限度地减少移植相关的发病率，在非清髓性、相关hla -单倍体（haplo）骨髓移植（BMT）移植后环磷酰胺的II期临床试验的背景下，开展了多机构学习合作。所有符合条件的参与者都有血红蛋白SS， 89%（16 / 18）有可识别的供体。患者年龄中位数为20.9岁（IQR, 12.1 ~ 26.0岁），移植最常见的指征是明显的脑卒中（占69%；16人中有11人）。在前3例患者中，调理方案包括抗胸腺细胞球蛋白、氟达拉滨、环磷酰胺和低剂量全身照射。移植物抗宿主病（GVHD）预防包括移植后环磷酰胺、霉酚酸酯和西罗莫司。3例患者中有2例（67%）发生了原发性移植排斥反应，这触发了研究停止规则。为了降低移植排斥风险，在调节方案中加入硫替帕，然后15例患者（包括2例既往移植排斥）在硫替帕增强调节方案中接受单倍体移植。在中位随访13.3个月（四分位数范围[IQR]， 3.8至23.1个月），93%的患者（15例中的14例）在6个月时获得了95%稳定的供体移植，总生存率为100%。中性粒细胞移植（>500）的中位时间为22天（IQR， 19 ~ 27天），血小板移植（>50 × 109(9/L)）的中位时间为28天（IQR， 27天至未达到）。2例患者为III-IV级急性GVHD， 1例患者为轻度慢性GVHD， 86%的患者（7例中的6例）在移植后1年停止免疫抑制治疗。我们的数据表明，单倍体移植联合环磷酰胺和硫替帕可以改善供体移植，而不会显著增加发病率或死亡率，并且可以显著扩大SCD患者的治疗选择。(C) 2018年美国血液和骨髓移植学会。
Curative therapy for individuals with severe sickle cell disease (SCD) who lack an HLA-identical sibling donor has been frustratingly elusive. In with the goal of improving engraftment while minimizing transplantation-related morbidity, a multi-institutional learning collaborative was developed in the context of a Phase II clinical trial of nonmyeloablative, related HLA-haploidentical (haplo) bone marrow transplantation (BMT) with post-transplantation cyclophosphamide. All eligible participants had hemoglobin SS, and 89% (16 of 18) had an identifiable donor. The median patient age was 20.9 years (IQR, 12.1 to 26.0 years), and the most common indication for transplantation was overt stroke (in 69%; 11 of 16). In the first 3 patients, the conditioning regimen consisted of antithymocyte globulin, fludarabine, cyclophosphamide, and low-dose total body irradiation. Graft-versus-host disease (GVHD) prophylaxis included post-transplantation cyclophosphamide, mycophenolate mofetil, and sirolimus. Primary graft rejection occurred in 2 of the 3 patients (67%), which triggered the study-stopping rule. To reduce graft rejection risk, thiotepa was added to the conditioning regimen, and then 15 patients (including 2 with previous graft rejection) underwent haplo-BMT with this thiotepa-augmented conditioning regimen. At a median followup of 13.3 months (interquartile range [IQR], 3.8 to 23.1 months), 93% (14 of 15) had >95% stable donor engraftment at 6 months, with 100% overall survival. The median time to neutrophil engraftment (>500) was 22 days (IQR, 19 to 27 days), and that for platelet engraftment (>50 x 109(9/L) was 28 days (IQR, 27 days to not reached). Two patients had grade III-IV acute GVHD, 1 patient had mild chronic GVHD, and 86% of patients (6 of 7) were off immunosuppression therapy by 1-year post-transplantation. Our data suggest that haplo-BMT with post-transplantation cyclophosphamide and thiotepa improves donor engraftment without significantly increasing morbidity or mortality and could dramatically expand curative options for individuals with SCD. (C) 2018 American Society for Blood and Marrow Transplantation.